Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Thromb Res. 2020 Sep;193:180-189. doi: 10.1016/j.thromres.2020.07.029. Epub 2020 Jul 15.
Atrial fibrillation (AF) is associated with a 5-fold increased risk of thromboembolic stroke. Extracellular vesicles (EVs) convey pathophysiological information and are possible biomarkers for risk of stroke.
EVs were measured in 836 patients with AF (of which 280 were stroke cases) selected from the ARISTOTLE trial and in a cohort of unselected 70 year old individuals (n = 1007, reference material). EVs from platelets, leukocytes, erythrocytes and inflammatory endothelial cells were measured using flow cytometry and a solid-phase proximity ligation assay.
Concentrations of EVs were higher in the ARISTOTLE patients than in the PIVUS cohort for all the EV groups except EVs from endothelial cells (p < 0.0001). The distributions of the concentrations of the EVs were similar among the control group and the stroke cases for all of the sources of EVs in the ARISTOTLE study. EVs were modestly correlated with the levels of NT-ProBNP, Cystatin C, GDF-15 and D-dimer. Stronger correlations were found for platelet EVs as well as phosphatidyl serine positive EVs that were correlated with CD40 ligand in the ARISTOTLE study. Leukocyte EVs were correlated with IL-6 in both the ARISTOTLE and the PIVUS study, implicating them in different physiological processes.
Higher levels of EVs were found in anticoagulated patients with AF and a higher risk of stroke than in a general population of similar age, possibly due to the high disease burden in AF patients. Our data with EVs representing a broad repertoire of activated blood cells in AF patients suggest that EVs are likely not a key mediator of occurrence of stroke in this population.
心房颤动（AF）与血栓栓塞性中风的风险增加 5 倍有关。细胞外囊泡（EVs）传递病理生理信息，可能是中风风险的生物标志物。
从 ARISTOTLE 试验中选择的 836 例 AF 患者（其中 280 例为中风病例）和未选择的 70 岁个体队列（n=1007，参考材料）中测量 EVs。使用流式细胞术和固相邻近连接测定法测量血小板、白细胞、红细胞和炎症内皮细胞的 EVs。
与 PIVUS 队列相比，除内皮细胞 EVs 外（p<0.0001），ARISTOTLE 患者的 EVs 浓度在所有 EV 组中均较高。在 ARISTOTLE 研究中，对于所有 EV 来源，对照组和中风病例的 EVs 浓度分布相似。EVs 与 NT-ProBNP、胱抑素 C、GDF-15 和 D-二聚体水平呈中度相关。在 ARISTOTLE 研究中，血小板 EVs 以及与 CD40 配体相关的 PS 阳性 EVs 与 NT-ProBNP 相关性更强。白细胞 EVs 与 ARISTOTLE 和 PIVUS 研究中的 IL-6 相关，表明它们参与了不同的生理过程。
与年龄相似的一般人群相比，抗凝治疗的 AF 患者和更高中风风险的患者中发现 EVs 水平更高，这可能是由于 AF 患者的疾病负担较高。我们使用代表 AF 患者广泛激活血细胞的 EVs 的数据表明，EVs 不太可能是该人群中风发生的主要介导物。
